Captopril is effective in the treatment of hypertension of all grades of severity. H2-receptors antagonists block gastric acid secretion and some cardiovascular effects of histamine. In view of the fact that, simultaneous administration of both drugs may alter the antihypertensive effect of captopril, present paper deals with the in vitro availability studies of captopril in presence of commonly used H2-receptor antagonists like cimetidine, ranitidine and famotidine. In order to simulate various pH levels in GI tract and to find out the kinetics and energetics of captopril-H2-receptor antagonist interactions, these studies were carried out in buffers of pH 4, 7.4 and 9 at 37 degrees C and at elevated temperatures. These studies clearly indicate that most of the H2-receptor antagonists bind to captopril, forming charge-transfer complexes. As a result, the availability of captopril was affected by the concurrent administration of H2-receptor antagonists. Accordingly coadministration of both the drugs should be avoided.